Skip to main content
SpringerLink
Log in

CD72 Polymorphism Associated with Child-Onset of Idiopathic Thrombocytopenic Purpura in Chinese Patients

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Idiopathic thrombocytopenic purpura (ITP) is a disease putatively relating to abnormal immune function and auto-antiplatelet immunoglobulin. We examined whether polymorphism of CD72, an inhibitory receptor of B cells, affect the susceptibility to ITP, or associated with the clinical characteristics of ITP. A case-control study was carried out in 206 Chinese ITP patients and 169 healthy controls. The detection of variable number of tandem repeats in CD72 intron 8 was performed by polymerase chain reaction and subsequent analysis with polyacrylamide gel electrophoresis. We did not find direct association between CD72 genotypes and susceptibility to ITP. The haplotype that contained one repeat of 13 nucleotides in intron 8 (designated as *1, and haplotype containing two repeat of 13 nucleotides in intron 8 is designated as *2) was significantly associated with early first onset age (≤14) in ITP patients (P = 0.03). ITP patients with CD72*1\*1 and *1\*2 genotype had a 3.09-fold [95% confidence interval (CI), 1.32~7.25] and 1.98-fold (95%CI, 0.92~4.25) increased risk of appearing ITP manifestation at their childhood respectively. The haplotype CD72*1 is apparently a risk allele, whereas CD72*2 a protective allele for child-onset of ITP disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002;346:995–1008.

    Article  PubMed  Google Scholar 

  2. Yang R, Han ZC. Pathogenesis and management of chronic idiopathic thrombocytopenic purpura: an update. Int J Hematol 2000;71:18–24.

    PubMed  CAS  Google Scholar 

  3. Zhou B, Zhao H, Yang RC, Han ZC. Multi-dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol 2005;54:107–16.

    Article  PubMed  Google Scholar 

  4. Berchtold P, Wenger M. Autoantibodies against platelet glycoproteins in autoimmune thrombocytopenic purpura: Their clinical significance and response to treatment. Blood 1993;81:1246–50.

    PubMed  CAS  Google Scholar 

  5. Hou M, Lv B, He Q, Lu L, Shi Y, Ji X, et al. Both splenic CD5(+) B and CD5(−) B cells produce platelet glycoprotein-specific autoantibodies in chronic ITP. Thromb Res 2003;110(1):1–5.

    Article  PubMed  CAS  Google Scholar 

  6. Kuwana M, Okazaki Y, Kaburaki J, Ikeda Y. Detection of circulating B cells secreting platelet-specific autoantibody is useful in the diagnosis of autoimmune thrombocytopenia. Am J Med 2003;114(4):322–5.

    Article  PubMed  Google Scholar 

  7. Ogawara H, Handa H, Morita K, Hayakawa M, Kojima J, Amagai H, et al. High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura. Eur J Haematol 2003;71:283–8.

    Article  PubMed  CAS  Google Scholar 

  8. Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, et al. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood 2004;103:2645–7.

    Article  PubMed  CAS  Google Scholar 

  9. Andersson PO, Olsson A, Wadenvik H. Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura. Br J Heamatol 2002;116:862–7.

    Article  CAS  Google Scholar 

  10. Kalwak K, Gorczyńska E, Wójcik D, Toporski J, Turkiewicz D, Slociak M, et al. Late-onset idiopathic thrombocytopenic purpura correlates with rapid B-cell recovery after allogeneic T-cell-depleted peripheral blood progenitor cell transplantation in children. Transplant Proc 2002;34(8):3374–7.

    Article  PubMed  CAS  Google Scholar 

  11. Gesundheit B, Cividalli G, Freeman A, Yatziv S, Koren G, Baruchel S. Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children. Eur J Haematol 2001;66(5):347–51.

    Article  PubMed  CAS  Google Scholar 

  12. Zver S, Zupan IP, Cernelc P. Cyclosporin A as an immunosuppressive treatment modality for patients with refractory autoimmune thrombocytopenic purpura after splenectomy failure. Int J Hematol 2006;83(3):238–42.

    Article  PubMed  Google Scholar 

  13. Patel K, Berman J, Ferber A, Caro J. Refractory autoimmune thrombocytopenic purpura treatment with Rituximab. Am J Hematol 2001;67(1):59–60.

    Article  PubMed  CAS  Google Scholar 

  14. Zaja F, Iacona I, Masolini P, Russo D, Sperotto A, Prosdocimo S, et al. B-cell depletion with rituximab as treatment for immune hemolytic anemia and chronic thrombocytopenia. Haematologica 2002;87(2):189–95.

    PubMed  CAS  Google Scholar 

  15. Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein MA, Leonard JP, Amadori S, et al. The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol 2004;125(2):232–9.

    Article  PubMed  CAS  Google Scholar 

  16. Taube T, Schmid H, Reinhard H, von Stackelberg A, Overberg US. Effect of a single dose of rituximab in chronic immune thrombocytopenic purpura in childhood. Haematologica 2005;90(2):281–3.

    PubMed  Google Scholar 

  17. Michael RG. To make antibodies or not: signaling by the B-cell antigen receptor. Trends Pharmacol Sci 2002;23:316–24.

    Article  Google Scholar 

  18. Valerie K, Sara F, Georges L, et al. Antigens varing in affinity for the B cell receptor induce differential B lymphocyte reponses. J Exp Med 1998;188:1453–64.

    Article  Google Scholar 

  19. Rock KL, Benacerraf B, Abbas AK. Antigen presentation by hapten-specific B lymphocytes. Role of serface immunoglobulin receptors. J Exp Med 1984;160:1002.

    Google Scholar 

  20. Tony HP, Parker DC. Major histocompatibility complex-restricted polyclonal B cell responses resulting from helper T cell recognition of anti-immunoglobulin presented by small B lymphocytes. J Exp Med 1985;161:223.

    Article  PubMed  CAS  Google Scholar 

  21. Casten LA, Kaumaya P, Pierce SK. Enhanced T cell responses to antigenic peptides targeted to B cell surface Ig, Ia or class I molecules. J Exp Med 1988;168:171.

    Article  PubMed  CAS  Google Scholar 

  22. Lars N. The role of CD22 and other inhibitory coreceptors in B-cell activation. Curr Opin Immunol 2005;17:290–7.

    Article  Google Scholar 

  23. Pan C, Baumgarth N, Parnes JR. CD72-deficient mice reveal nonredundant roles of CD72 in B cell development and activation. Immunity 1999;11:495–506.

    Article  PubMed  CAS  Google Scholar 

  24. Adachi T, Wakabayashi C, Nakayama T, Yakura H, Tsubata T. CD72 negatively regulates signaling through the antigen receptor of B cells. J Immunol 2000;164:1223–9.

    PubMed  CAS  Google Scholar 

  25. Adachi T, Wienands J, Wakabayashi C, Yakura H, Reth M, Tsubata T. SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates. J Biol Chem 2001;276:26648–55.

    Article  PubMed  CAS  Google Scholar 

  26. Wakabayashi C, Adachi T, Wienands J, Tsubata T. A distinct signaling pathway used by the IgG-containing B cell antigen receptor. Science 2002;298:2392–5.

    Article  PubMed  CAS  Google Scholar 

  27. Rojas A, Xu F, Rojas M, Thomas JW. Structure and function of CD72 in the non-obese diabetic (NOD) mouse. Autoimmunity 2003;36:233–9.

    Article  PubMed  CAS  Google Scholar 

  28. Qu WM, Miyazaki T, Terada M, Lu LM, Nishihara M, Yamada A, et al. Genetic dissection of vasculitis in MRL/lpr lupus mice: a novel susceptibility locus involving the CD72c allele. Eur J Immunol 2000;30(7):2027–37.

    Article  PubMed  CAS  Google Scholar 

  29. Hitomi Y, Tsuchiya N, Kawasaki A, Ohashi J, Suzuki T, Kyogoku C, et al. CD72 polymorphisms associated with alternative splicing modify susceptibility to human systemic lupus erythematosus through epistatic interaction with FCGR2B. Human Mol Gen 2004;13:2907–17.

    Article  CAS  Google Scholar 

  30. Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T cells profile in chronic idiopathic thrombocytopenic purpura. Heamatologica 2005;90:914–23.

    Google Scholar 

  31. Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, et al. Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signalling. Immunity 2000;13:621–31.

    Article  PubMed  CAS  Google Scholar 

  32. Li DH, Tung JW, Tarner IH, Snow AL, Yukinari T, Ngernmaneepothong R, et al. CD72 Down-Modulates BCR-Induced Signal Transduction and Diminishes Survival in Primary Mature B Lymphocytes. J Immunol 2006;176:5321–8.

    PubMed  Google Scholar 

  33. Venkataraman C, Muthusamy N, Muthukkumar S, Bondada S. Activation of lyn, blk, and btk but not syk in CD72-stimulated B lymphocytes. J Immunol 1998;160:3322–9.

    PubMed  CAS  Google Scholar 

  34. Venkataraman C, Lu PJ, Buhl AM, Chen CS, Cambier JC, Bondada S. CD72-mediated B cell activation involves recruitment of CD19 and activation of phosphatidylinositol 3-kinase. Eur J Immunol 1998;28:3003.

    Article  PubMed  CAS  Google Scholar 

  35. Olsson B, Andersson PO, Jernas M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003;9:1123–4.

    Article  PubMed  CAS  Google Scholar 

  36. Hopkins LM, Davis JM, Buchli R, Vangundy RS, Schwartz KA, Gerlach JA. MHC class I-associated peptides identified from normal platelets and from individuals with idiopathic thrombocytopenic purpura. Hum Immunol 2005;66:874–83.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This project was supported in part by grants of National Natural Science Foundation of China (30670900). Ministry of Education of China (20060023031), Ministry of Personnel of China (2006), and Tianjin Key Project for Basic Research (06YFJZJC01800). The authors would like to thank Prof. Man-Chiu Poon (University of Calgary, Canada) for critical review the manuscript.

Author information

Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin, 300020, China

    Jianhui Xu, Shihong Lu, Jie Tao, Zeping Zhou, Zhenping Chen, Ying Huang & Renchi Yang

Authors
  1. Jianhui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shihong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zeping Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhenping Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renchi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Renchi Yang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, J., Lu, S., Tao, J. et al. CD72 Polymorphism Associated with Child-Onset of Idiopathic Thrombocytopenic Purpura in Chinese Patients. J Clin Immunol 28, 214–219 (2008). https://doi.org/10.1007/s10875-007-9158-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-007-9158-z

Keywords

Search

Navigation